Long-Term Lithium Therapy for Bipolar Disorder: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Abstract
Objective The authors sought to determine the efficacy and acceptability of lithium for relapse prevention in bipolar disorder. Method A systematic review and meta-analysis of randomized controlled trials comparing lithium with placebo in the long-term treatment of bipolar disorders was conducted. Data were obtained from searching the registers of the Cochrane Collaboration; reviewing reference lists, journals, and conference abstracts; and contacting authors, experts, and pharmaceutical companies. Outcomes investigated included risk of relapse (manic, depressive, and total) as well as risk of specific adverse effects and total withdrawal rates. Results Five randomized controlled trials (770 participants) were included. Lithium was more effective than placebo in preventing all relapses (random effects relative risk=0.65, 95% CI=0.50 to 0.84) and manic relapses (relative risk=0.62, 95% CI=0.40 to 0.95). The protective effect of lithium on depressive relapses was smaller and was less robust (relative risk=0.72, 95% CI=0.49 to 1.07). Conclusions Lithium treatment reduces the risk of relapse in bipolar disorder. The preventive effect is clear for manic episodes, although it is equivocal for depressive episodes.
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Publication bias might be particularly important in a review including studies with small numbers of events and small size of the trials, because only one or two moderately sized trials with neutral or negative results could materially affect the estimates.
“Publication bias might be particularly important in a review including studies with small numbers of events and small size of the trials, because only one or two moderately sized trials with neutral or negative results could materially affect the estimates.26”
From Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis (2013) · cites this paper as [26]
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- Authors
- Geddes, J. R., Burgess, S., Hawton, K., Jamison, K., & Goodwin, G. M.
- Affiliations
- Warneford Hospital (GB)
- Venue
- American Journal of Psychiatry
- Published
- 2004-02-01
- Volume
- 161
- Issue
- 2
- Pages
- 217-222
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2099017168
- Cited by
- 661
- References
- 4
- Citations by year
- 2026: 22 · 2025: 17 · 2024: 21 · 2023: 26 · 2022: 29 · 2021: 26 · 2020: 21 · 2019: 27 · 2018: 34 · 2017: 28 · 2016: 36 · 2015: 28 · 2014: 47 · 2013: 35 · 2012: 38
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- lithium, bipolar disorder, long-term lithium therapy, relapse prevention, manic relapse, depression relapse, treatment efficacy, adverse effects, drug withdrawal, treatment acceptability
- MeSH terms
- Bipolar Disorder, Humans, Time, Randomized Controlled Trials as Topic, Lithium Carbonate, Antimanic Agents, Secondary Prevention
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